This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Vulnerable plaques are characterized by morphological features such as a thin fibrous cap, a large necrotic core, superficial foam cells, and intraplaque hemorrhage. We propose the use of a combination of multiple spectroscopic methods, including Raman, diffuse reflectance, and intrinsic fluorescence spectroscopy, to detect these key morphological markers of vulnerable plaque. We refer to the combined technique as multimodal spectroscopy (MMS). A preliminary study was performed in vitro on 17 human carotid artery specimens. Following the acquisition of the spectra, each specimen was histologically evaluated. It was determined that parameters obtained from diffuse reflectance spectroscopy, the hemoglobin concentration, can potentially be used to detect intraplaque hemorrhage. A parameter extracted from the intrinsic fluorescence that relates to the amount of collagen in the topmost layers of the tissue can be used to sense the presence of a thin fibrous cap. Finally, a Raman spectroscopy parameter related to the amount of cholesterol and necrotic material can potentially be used to detect a necrotic core. The MMS method shows great promise to provide complementary morphological information about plaque composition.